title: A change from stimulatory to blocking antibody activity in Graves' disease during pregnancy.
abstract: Remission of Graves' disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associated with type 2 rather than type 1 cytokine production, a decrease in thyroid-stimulating antibody (TSAb) activity alone is unlikely to account for the remission during pregnancy. We hypothesized that a change in the antibody characteristics may occur as pregnancy advances. Fifteen women were studied in the first, second, and third trimesters of pregnancy and 4 months postpartum. TSH receptor antibodies were determined using human thyroid cell cultures, and lymphocyte subsets were measured by flow cytometry. Median TSAb (determined by cAMP release) decreased from 280% (96-3200) to 130% (range, 35-350; P < 0.05) during pregnancy, but no significant change was noted with the TSH binding inhibitory antibody (TBII; determined by RRA). Thyroid stimulation-blocking antibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased from 16 +/- 9% to 43 +/- 16% (mean +/- SD; P < 0.005). The increase in TSBAb was observed even among those patients who were in clinical remission before pregnancy. Overall, a negative correlation was observed between TSBAb activities and free T4 levels during pregnancy (r = -0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were observed in the seven patients who relapsed during the postpartum period. In comparison, the healthy pregnant women (n = 14) were all negative for TSAb, TBII, and TSBAb throughout pregnancy. The absolute number of T lymphocytes, T helper cells, and natural killer cells, but not B cells, decreased significantly during pregnancy in both healthy women and GD patients. GD patients had significantly more CD5+ B cells at all stages of pregnancy compared to controls. In conclusion, a change in specificity from stimulatory to blocking antibodies was observed in GD patients during pregnancy and may contribute to the remission of GD during pregnancy.
authors.affiliation: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Republic of China.
authors.forename: A W
authors.initials: AW
authors.lastname: Kung
authors.forename: B M
authors.initials: BM
authors.lastname: Jones
mesh_terms: D019138:Antibodies, Blocking / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D002478:Cells, Cultured; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood* / Q000276:immunology; D007694:Killer Cells, Natural; D018655:Lymphocyte Count; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D011446:Prospective Studies; D011989:Receptors, Thyrotropin / Q000097:blood*; D012075:Remission, Spontaneous; D013601:T-Lymphocytes; D006377:T-Lymphocytes, Helper-Inducer; D013974:Thyroxine / Q000097:blood
chemical_list: D019138:Antibodies, Blocking; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; C094372:thyrotropin-binding inhibitory immunoglobulin; D013974:Thyroxine